The role of complement C3 opsonization, C5a receptor, and CD14 in E. coli-induced up-regulation of granulocyte and monocyte CD11b/CD18 (CR3), phagocytosis, and oxidative burst in human
The role of complement C3 opsonization, C5a receptor, and CD14 in E. coli-induced up-regulation of granulocyte and monocyte CD11b/CD18 (CR3), phagocytosis, and oxidative burst in human
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DOI：
10.1189/jlb.0806538
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发表时间：
2007-06-01
影响因子：
5.5
通讯作者：
Mollnes, Tom E.
中科院分区：
文献类型：
--
作者：
Brekke, Ole-Lars;Christiansen, Dorte;Mollnes, Tom E.
研究了补体和CD 14在大肠杆菌诱导的人全血白细胞CD 11b上调、吞噬作用和氧化爆发中的相对作用。使用高度特异性凝血酶抑制剂来匹卢定作为抗凝剂，因为它不影响补体激活。在C3（抗C2和抗因子D）和C5（C5 a受体拮抗剂和抗C5/C5 a）水平的补体抑制有效地抑制粒细胞中的CD 11b上调、吞噬和氧化爆发。单核细胞活化通常较少依赖补体，但当C3活化被阻断时，获得了对吞噬作用和氧化爆发的显著抑制。只有抗-C2和抗-D因子联合使用才能阻断E. coliC 3蛋白完全变性。全E。coli、破碎的E.大肠杆菌，和C3-转化酶激活剂眼镜蛇毒因子上调CD 11b迅速对这两种细胞类型，成比例的补体激活潜力的流体相。相比之下，纯化的LPS浓度与E.大肠杆菌制剂不激活补体。氧化爆发仅由全菌引起。最后，补体抑制和抗CD 14的组合完全阻断了E.大肠杆菌诱导的粒细胞和单核细胞CD 11b上调和定量，几乎取消吞噬作用。结果表明，补体和CD 14，尽管对粒细胞和单核细胞的不同作用，是两个关键的，定量因素负责E。大肠杆菌诱导的CD 11b，吞噬作用和氧化爆发在两种细胞类型。
The relative role of complement and CD14 in Escherichia coli-induced leukocyte CD11b up-regulation, phagocytosis, and oxidative burst in human whole blood was examined. The highly specific thrombin inhibitor lepirudin was used as anticoagulant, as it does not affect complement activation. Complement inhibition at the level of C3 (anti-C2 and anti-factor D) and C5 (C5a receptor antagonist and anti-C5/C5a) efficiently inbibited CD11b up-regulation, phagoeytosis, and oxidative burst in granulocytes. Monocyte activation was generally less complement-dependent, but when C3 activation was blocked, a pronounced inhibition of phagocytosis and oxidative burst was obtained. Only the combination of anti-C2 and antifactor D blocked E. coli C3 opsoinization completely. Whole E. coli, disrupted E. coli, and the C3-convertase activator cobra venom factor upregulated CD11b rapidly on both cell types, proportional to their complement activation potential in the fluid phase. In comparison, purified LPS at concentrations comparable with that present in the E. coli preparations did not activate complement. Oxidative burst was induced only by whole bacteria. Finally, the combination of complement inhibition and anti-CD14 completely blocked E. coli-induced granulocyte and monocyte CD11b up-regulation and quantitatively, virtually abolished phagocytosis. The results indicate that complement and CD14, despite differential effects on granulocytes and monocytes, are the two crucial, quantitative factors responsible for E. coli-induced CD11b, phagocytosis, and oxidative burst in both cell types.